The search for the ideal blood vessel substitute has to date focused on biological tissues and synthetics. Variations upon simple substitutions with these materials have included such innovations as heparin bonding, endothelial coating with cells grown in tissue culture, and in vivo collagen tube formation on silicone mandrels. Despite intensive efforts to improve the nature of blood vessel substitutes many problems remain, such as increasing failure rate with decreasing caliber of the blood vessel substitute, a high failure rate when infection supervenes, biological failure or degradation by fibrin layering, intimal and subintimal hyperplasia, and aneurysm formation.
A major problem in vascular reconstructive surgery is how to effectively supply blood to organs and tissues whose blood vessels are inadequate either through congenital defects or acquired disorders such as trauma, arteriosclerosis and other diseases. Various techniques and materials have been devised to excise and replace blood vessels, to bypass blood vessels, and to patch, i.e., widen the channels of vessels. Initially, arterial homografts (human arteries) were used to restore continuity; however, limited supply, inadequate sizes, development of aneurysms and arteriosclerosis necessitated the search for a better substitute.
A great advance was the development of the partially porous and pliable synthetic plastic cloth. Synthetic fibers frequently used as graft material include polyethylene terephthalate (Dacron.RTM.) and polytetrafluoroethylene (Teflon.RTM.). Some of the problems experienced with the use of artificially constructed grafts include: (1) infection leading to hemorrhage, sepsis and/or death; (2) the inner lining of the graft is thrombogenic, so that it is predisposed to clotting which may result in total occlusion of the graft and distal embolism of the clot; (3) the rigidity of fabric grafts may result in twisting and kinking especially where a joint is crossed leading to graft occlusion; (4) because of clotting difficulties, smaller caliber artificial grafts are frequently unsuccessful. Grafts smaller than about 5 mm in inside diameter almost invariably becomes blocked by clots which form therein, and clotting difficulties arise in certain bodily locations even with vascular grafts having inside diameters as great as 10 mm. Moreover, a delicate balance must be struck in the porosity of the synthetic graft since the wall thereof must be sufficiently porous to permit ingrowth and deposition of fibrin so that eventually the wall is covered with scar tissue both internally and externally and yet not be so porous that hemorrhage occurs. This makes it necessary to pre-clot the knitted graft prior to use. Many problems posed by artificially manufactured prostheses have led investigators to seek newer and better methods. These include new techniques of "cleaning out" an artery such as by carbodissection, dilating arteries, development of bovine heterografts, and creating collagen tubes by inserting a mandrel within the recipient for later use of a graft.
It is known that homografts have been used for vascular grafting with considerable success. Commonly, the saphenous vein has been used in cases where the patient is the donor (an autograft) and where another human is a donor (allograft). These vessels require no treatment before implantation; however, they present problems of unavailability, disparity in size, nonuniformity of caliber, presence of valves and varicosities, and the need for additional authorization in the case of allografts. The removal of the saphenous vein to be used for vascular grafting in the same patient involves keeping the patient on the operating table for a substantially longer time. Moreover, the operation is quite delicate and sometimes is a failure. Finally, where rejection is a problem and the patient needs further grafting after the patient's own saphenous veins have been removed, repair by this method becomes impossible.
In a prior invention of applicant, a combined biologicsynthetic vascular graft consisting of umbilical cord vessels surrounded by a synthetic mesh support is provided. The vessels in the human umbilical cord are separated, treated according to the process described in U.S. Pat. 3,974,526 and used as grafts in vascular reconstructive surgery.
Traditionally discarded after division from the infant at birth, the umbilical cord here has found a new use as the source of valuable grafting materials. It is composed of a vein and two arteries surrounded by a sticky jelly-like substance called Wharton's jelly all encased in the surrounding tissue. The cord varies in length from inches to over three feet in length and is highly flexible. Both the arteries and veins contained therein are suitable for use in vascular surgery. The umbilical cord is fetal tissue in a primitive state giving it the advantage that antigenicity is lower than in adult tissue.
The umbilical cord may be used fresh or it may be preserved for future use. The cord may be freeze-dried, refrigerated, chemically stored or preserved in other known ways. It may require treatment with antibiotics, chemicals, drugs, X-rays and temperature to insure that it is sterile when ready for use. It is antigen and may require chemical or other known treatment to remove any antigen substances. Coiled at the time of delivery, the cord can be straightened out by mechanical or chemical techniques. Cords obtained from mammals, premature babies, early or terminated pregnancies can also be used to repair smaller vessels.
Until the above-noted discovery, the unique morphology of umbilical cord vessels appeared to render them unsuitable grafting materials. The one vein and two arteries in these cords are located together within the protective tissue of the cord; the arteries spiral around the vein in a helical fashion, an occurrence unique in vascular anatomy. This arrangement apparently results in reduced kinking and twisting. Once separated and treated according to the process described in U.S. Pat. No. 3,974,526, the vessels are straight yet remain flexible. They can be shaped to meet the specific needs of the recipient by adjusting the width and length. The grafts as prepared can be used as both arterial and venous substitutes; furthermore, they can be used to patch and repair diseased vessels of the body. Finally, it should be noted that the availability of umbilical cords represents a virtually unlimited supply of grafting material in connection with the present invention.
The umbilical cord vessels, especially the arteries, frequently contain valves known as the valves of Hoboken. The presence of these "valves" is one of the factors which has made it unobvious to previous investigators to use these vessels as tubular grafts. Within the present process of preparing a cord for prosthetic use, the valves are treated and eliminated so as to create an unconstricted inner surface within the vessels.
The vessels used as grafts herein are commonly three feet in length thereby eliminating the need for joining several shorter grafts often necessary in vascular surgery involving the arteries or veins of the leg. The diameter of the vessel can also be adjusted by shrinking the vessel during the preparation process and the wall thickness of the vein can also be controlled during the separation step by the amount of tissue removed. The tubes may be slit open longitudinally to obtain a planar graft or patch for repairing vessels of the body. The grafts may be tapered to closely conform in shape to the body's natural vessels.
Tapering also eliminates a major problem associated with autogenous vein grafts as arterial substitutes. Since the saphenous vein contains valves which direct blood flow toward the heart, these grafts must be reversed when used to replace an artery, resulting in a graft which is tapered in the opposite direction to that of the original or host vessel. The graft of applicant's invention is valveless and readily can be shaped and tapered to the recipient's needs. The need for additional operations, as in the use of autogenous vein grafts such as the saphenous vein, is obviated by the use of these umbilical cord grafts. Such operations to obtain the patient's own vein involve the added risks of prolonged anesthesia, infection, disease and death to the donor.
The advantages of using umbilical cord veins and arteries as vascular grafts may be summarized as follows:
1) availability of grafting material which usually is obtained under sterile conditions (i.e. the operating room at delivery time);
2) ability to be shaped and tapered;
3) absence of valves or branches;
4) flexibility such that the graft can be used across joints;
5) low antigenicity which can be eliminated by the process;
6) use in small vessels without leading to thrombosis;
7) these thin-walled porous vessels permit hardening and tanning agents to penetrate easily during processing; and
8) the graft is entirely preformed, complete when implanted, and may contain an outer mesh support which allows for easy ingrowth of extra fibrocollagenous tissue from outside the graft.
The process in applicant's U.S. Pat. No. 3,974,526, eliminates antigenicity, hardens and strengthens the graft, removes the valves of Hoboken and any varicosities in the vessels, and shapes the vessel to any shape desired. The graft obtained is straight, flexible and can be twisted in any direction. This is a major advantage over autogenous vein grafts which must be implanted in their original shape to avoid minor twists which can lead to closure of the vessel when blood begins to flow through.
Finally, the use of the veins and arteries of the umbilical cord as vascular substitutes has the following advantages during surgical implantation:
1) operating room time (of autografts for example) can be reduced by one to two hours since the need for multiple incisions and the attendant additional procedures are eliminated;
2) a suitable tapered diameter makes it easy to implant the vessel to fit the host vessel to which it is attached:
3) the graft is sutured easily and with a minimum bleeding from the needle insertion hole;
4) the lumen of the graft following treatment remains open and does not collapse as does the saphenous vein; and
5) a needle can be inserted into the interstices of the mesh support without harming the graft.
A process for producing a tubular prosthesis for vascular reconstructive surgery, of the type described in U.S. Pat. No. 3,974,526 comprises the following steps: (a) cleansing the veins and arteries of the umbilical cord to remove blood and residual fluids; (b) removing Wharton's jelly from within the cord; (c) mechanically separating the two arteries and vein from the cord and from one another; (d) eliminating the valves of Hoboken within the vessel; (e) inserting a mandrel to shape the vessel; (f) treating the vessel with a hardening or tanning agent; (g) treating the vessel with an antithrombogenic agent; (h) applying a mesh support externally to the vessels; and (i) implanting the graft so formed.
The prosthesis produced according to this process is intended for use in vascular reconstructive surgery of animals including humans, primates and mammals. It may be used to repair, replace or augment a diseased or defective vein or artery of the body. The thin walled graft may be used as a substitute for the ureter, bile duct and other organs of the body.
Cleansing, rinsing or irrigating solutions which may be employed include water, sterile saline solution, Ringer's lactate solution, hydrogen peroxide, sodium bicarbonate solution, alcohol, and transplantation perfusate solutions.
Antithrombogenic agents which may be used to treat the graft include L-sodium glutamate, L-alanine, L-phenylalanine, L-cysteine, L-lysine.
Wharton's jelly may be removed mechanically or chemically using hyaluronidase to dissolve the hyaluronic acid which comprises the jelly.
The arteries are separated from the cord by passing an instrument between the arteries and the outer cord tissue. To separate the vein from the umbilical cord, a mandrel is inserted through the lumen of the vein and said mandrel is fixed in a vise like mechanism which permits rotation of the cord in order to separate the arteries which are spirally around the vein. The valves of Hoboken are eliminated by forcing a fluid through the lumen of the vein or artery. The fluid may be Ringer's lactate solution, gluteraldehyde, sterile saline solution, water or transplantation perfusate solution.
The mandrel inserted to shape the vessels and remove the remaining valves of Hoboken may be constructed of an inert material which will not react with the graft vessel or chemicals used in the process. For these purposes glass, silicone, stainless steel or plastic may be used. The mandrel may be straight or curved, solid or hollow, cylindrical or tapered, and smooth or perforated on its surface.
Hardening or tanning agents which may be used to shrink, dilate or otherwise shape the vessel include aldehydes such as glutaraldehyde, dialdehyde starch and formaldehyde, hydrous alcohol, glyoxal, and chronic oxide.
The mesh support applied to the shaped graft in Applicant's U.S. Pat. No. 3,974,526, may be made of any non-adsorbable synthetic material such as Dacron.RTM., Teflon.RTM., polyester, polypropylene, Mersilene mesh, plastic and cloth. The mesh is intended to provide support for the graft and should not be absorbed by it or the recipient host tissue readily. The material used must be sterile when implanted.